Alternating stealth polymer coatings between administrations minimizes toxic and antibody immune responses towards nanomedicine treatment regimens

Bin Li, Feng Chu, Qian Lu, Yiqing Wang, Lucas A. Lane

研究成果: 雜誌貢獻文章同行評審

4 引文 斯高帕斯(Scopus)

摘要

In efforts to achieve minimal systemic toxicity and high tumor delivery efficiencies in cancer therapy, various nanomedicine formulations having stealth polymer coatings have been developed for minimizing immune cell uptake and off-target macrophage phagocyte system (MPS) organ accumulation. Despite an initial reduction in immune cell uptake, stealth nanoparticles still initiate an antibody immune response. This response acts on subsequent administrations in treatment regimens resulting in accelerated blood clearance of particles into MPS organs, particularly the liver, where they are retained for prolonged periods. Consequently, doses after the first administration in treatment regimens have diminished tumor accumulation and increased MPS toxicity. Here, we present a strategy reducing antibody responses to each dose in a treatment regimen by alternating between polyethylene-glycol and polymethyloxazoline polymers as the nanoparticle coating between administrations. In a weekly dosing regimen, we find that the first dose of particles having either coating display similar favorable pharmacokinetics and biodistributions, thus allowing the polymers to be used interchangeably. However, when maintaining the same coating in subsequent administrations, we find that particles are in circulation at the height of the antibody immune response resulting in 50–60% decreases of circulation half-lives and tumor accumulation along with 50% increases in liver accumulation. By alternating the polymers used in the nanoparticle coating between administrations, we find each dose maintains favorable in vivo behaviors at the height of the antibody immune response to the previous administration. Furthermore, our strategy increases the clearance of particles uptaken by macrophages and hepatocytes, resulting in marked decreases in hepatotoxicity.
原文英語
頁(從 - 到)527-540
頁數14
期刊Acta Biomaterialia
121
DOIs
出版狀態已發佈 - 2月 2021
對外發佈

ASJC Scopus subject areas

  • 生物技術
  • 生物材料
  • 生物化學
  • 生物醫學工程
  • 分子生物學

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